Bcl-2 antisense (oblimersen sodium) plus dacarbazine in patients with advanced melanoma: The oblimersen melanoma study group

Agop Y. Bedikian, Michael Millward, Hubert Pehamberger, Robert Conry, Martin Gore, Uwe Trefzer, Anna C. Pavlick, Ronald DeConti, Evan M Hersh, Peter Hersey, John M. Kirkwood, Frank G. Haluska

Research output: Contribution to journalArticle

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Abstract

Purpose: Chemotherapy resistance in melanoma has been linked to antiapoptotic effects mediated by Bcl-2 protein. We evaluated whether targeting Bcl-2 using an antisense oligonucleotide (oblimersen sodium could improve the efficacy of systemic chemotherapy in patients with advanced melanoma. Patients and Methods: We randomly assigned chemotherapy-naïve patients with advanced melanoma to treatment with dacarbazine (1,000 mg/m2) alone or preceded by a 5-day continuous intravenous infusion of oblimersen sodium (7 mg/kg/d) every 3 weeks for up to eight cycles. Patients were stratified by Eastern Cooperative Oncology Group performance status, liver metastases, disease site, and serum lactate dehydrogenase (LDH). The primary efficacy end point was overall survival. Results: Among 771 patients randomly assigned, the addition of oblimersen to dacarbazine yielded a trend toward improved survival at 24-month minimum follow-up (median, 9.0 v 7.8 months; P = .077) and significant increases in progression-free survival (median, 2.6 v 1.6 months; P < .001), overall response (13.5% v 7.5%; P = .007), complete response (2.8% v 0.8%), and durable response (7.3% v3.6%; P = .03). A significant interaction between baseline serum LDH and treatment was observed; oblimersen significantly increased survival in patients whose baseline serum LDH was not elevated (median overall survival, 11.4 v 9.7 months; P = .02). Neutropenia and thrombocytopenia were increased in the oblimersen-dacarbazine group; however, there was no increase in serious infections or bleeding events. Conclusion: The addition of oblimersen to dacarbazine significantly improved multiple clinical outcomes in patients with advanced melanoma and increased overall survival in patients without an elevated baseline serum LDH.

Original languageEnglish (US)
Pages (from-to)4738-4745
Number of pages8
JournalJournal of Clinical Oncology
Volume24
Issue number29
DOIs
StatePublished - Oct 10 2006
Externally publishedYes

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Dacarbazine
Melanoma
L-Lactate Dehydrogenase
Survival
Serum
Drug Therapy
oblimersen
Antisense Oligonucleotides
Neutropenia
Intravenous Infusions
Thrombocytopenia
Disease-Free Survival
Liver Diseases
Hemorrhage
Neoplasm Metastasis
Therapeutics
Infection

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Bedikian, A. Y., Millward, M., Pehamberger, H., Conry, R., Gore, M., Trefzer, U., ... Haluska, F. G. (2006). Bcl-2 antisense (oblimersen sodium) plus dacarbazine in patients with advanced melanoma: The oblimersen melanoma study group. Journal of Clinical Oncology, 24(29), 4738-4745. https://doi.org/10.1200/JCO.2006.06.0483

Bcl-2 antisense (oblimersen sodium) plus dacarbazine in patients with advanced melanoma : The oblimersen melanoma study group. / Bedikian, Agop Y.; Millward, Michael; Pehamberger, Hubert; Conry, Robert; Gore, Martin; Trefzer, Uwe; Pavlick, Anna C.; DeConti, Ronald; Hersh, Evan M; Hersey, Peter; Kirkwood, John M.; Haluska, Frank G.

In: Journal of Clinical Oncology, Vol. 24, No. 29, 10.10.2006, p. 4738-4745.

Research output: Contribution to journalArticle

Bedikian, AY, Millward, M, Pehamberger, H, Conry, R, Gore, M, Trefzer, U, Pavlick, AC, DeConti, R, Hersh, EM, Hersey, P, Kirkwood, JM & Haluska, FG 2006, 'Bcl-2 antisense (oblimersen sodium) plus dacarbazine in patients with advanced melanoma: The oblimersen melanoma study group', Journal of Clinical Oncology, vol. 24, no. 29, pp. 4738-4745. https://doi.org/10.1200/JCO.2006.06.0483
Bedikian, Agop Y. ; Millward, Michael ; Pehamberger, Hubert ; Conry, Robert ; Gore, Martin ; Trefzer, Uwe ; Pavlick, Anna C. ; DeConti, Ronald ; Hersh, Evan M ; Hersey, Peter ; Kirkwood, John M. ; Haluska, Frank G. / Bcl-2 antisense (oblimersen sodium) plus dacarbazine in patients with advanced melanoma : The oblimersen melanoma study group. In: Journal of Clinical Oncology. 2006 ; Vol. 24, No. 29. pp. 4738-4745.
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abstract = "Purpose: Chemotherapy resistance in melanoma has been linked to antiapoptotic effects mediated by Bcl-2 protein. We evaluated whether targeting Bcl-2 using an antisense oligonucleotide (oblimersen sodium could improve the efficacy of systemic chemotherapy in patients with advanced melanoma. Patients and Methods: We randomly assigned chemotherapy-na{\"i}ve patients with advanced melanoma to treatment with dacarbazine (1,000 mg/m2) alone or preceded by a 5-day continuous intravenous infusion of oblimersen sodium (7 mg/kg/d) every 3 weeks for up to eight cycles. Patients were stratified by Eastern Cooperative Oncology Group performance status, liver metastases, disease site, and serum lactate dehydrogenase (LDH). The primary efficacy end point was overall survival. Results: Among 771 patients randomly assigned, the addition of oblimersen to dacarbazine yielded a trend toward improved survival at 24-month minimum follow-up (median, 9.0 v 7.8 months; P = .077) and significant increases in progression-free survival (median, 2.6 v 1.6 months; P < .001), overall response (13.5{\%} v 7.5{\%}; P = .007), complete response (2.8{\%} v 0.8{\%}), and durable response (7.3{\%} v3.6{\%}; P = .03). A significant interaction between baseline serum LDH and treatment was observed; oblimersen significantly increased survival in patients whose baseline serum LDH was not elevated (median overall survival, 11.4 v 9.7 months; P = .02). Neutropenia and thrombocytopenia were increased in the oblimersen-dacarbazine group; however, there was no increase in serious infections or bleeding events. Conclusion: The addition of oblimersen to dacarbazine significantly improved multiple clinical outcomes in patients with advanced melanoma and increased overall survival in patients without an elevated baseline serum LDH.",
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T1 - Bcl-2 antisense (oblimersen sodium) plus dacarbazine in patients with advanced melanoma

T2 - The oblimersen melanoma study group

AU - Bedikian, Agop Y.

AU - Millward, Michael

AU - Pehamberger, Hubert

AU - Conry, Robert

AU - Gore, Martin

AU - Trefzer, Uwe

AU - Pavlick, Anna C.

AU - DeConti, Ronald

AU - Hersh, Evan M

AU - Hersey, Peter

AU - Kirkwood, John M.

AU - Haluska, Frank G.

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N2 - Purpose: Chemotherapy resistance in melanoma has been linked to antiapoptotic effects mediated by Bcl-2 protein. We evaluated whether targeting Bcl-2 using an antisense oligonucleotide (oblimersen sodium could improve the efficacy of systemic chemotherapy in patients with advanced melanoma. Patients and Methods: We randomly assigned chemotherapy-naïve patients with advanced melanoma to treatment with dacarbazine (1,000 mg/m2) alone or preceded by a 5-day continuous intravenous infusion of oblimersen sodium (7 mg/kg/d) every 3 weeks for up to eight cycles. Patients were stratified by Eastern Cooperative Oncology Group performance status, liver metastases, disease site, and serum lactate dehydrogenase (LDH). The primary efficacy end point was overall survival. Results: Among 771 patients randomly assigned, the addition of oblimersen to dacarbazine yielded a trend toward improved survival at 24-month minimum follow-up (median, 9.0 v 7.8 months; P = .077) and significant increases in progression-free survival (median, 2.6 v 1.6 months; P < .001), overall response (13.5% v 7.5%; P = .007), complete response (2.8% v 0.8%), and durable response (7.3% v3.6%; P = .03). A significant interaction between baseline serum LDH and treatment was observed; oblimersen significantly increased survival in patients whose baseline serum LDH was not elevated (median overall survival, 11.4 v 9.7 months; P = .02). Neutropenia and thrombocytopenia were increased in the oblimersen-dacarbazine group; however, there was no increase in serious infections or bleeding events. Conclusion: The addition of oblimersen to dacarbazine significantly improved multiple clinical outcomes in patients with advanced melanoma and increased overall survival in patients without an elevated baseline serum LDH.

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